Control of hippocampal gamma oscillation frequency by tonic inhibition and excitation of interneurons

Abstract

Gamma-frequency oscillations depend on phasic synaptic GABAA receptor-mediated inhibition to synchronize spike timing. The spillover of synaptically-released GABA can also activate extrasynaptic GABAA receptors, and such tonic inhibition may also contribute to modulating network dynamics. In many neuronal cell types, tonic inhibition is mediated by δ subunit-containing GABAA receptors. We show that the frequency of in vitro cholinergically-induced gamma oscillations in the mouse hippocampal CA3 region is increased by the activation of NMDA receptors (NMDAR) on interneurons. The NMDAR-dependent increase of gamma oscillation frequency is counteracted by the tonic inhibition of the interneurons mediated by δ subunit-containing GABAA receptors. Recordings of synaptic currents during gamma activity show that NMDAR-mediated increases in oscillation frequency correlate with a progressive synchronization of phasic excitation and inhibition in the network. Thus, the balance between tonic excitation and tonic inhibition of interneurons may modulate gamma frequency by shaping interneuronal synchronization.

Tonic GABA A conductance bidirectionally controls interneuron firing pattern and synchronization in the CA3 hippocampal network

“…The present results suggest that tonic inhibition affects synchrony or power rather than the frequency of network oscillations, whereas a previous report found an inverse association of tonic conductance with the oscillation frequency rather than power (10). However, the earlier work used genetic deletion of the delta subunit-containing GABA A receptors as a tool to manipulate tonic conductance, which might subtly shift the network excitability away from the biphasic mode.…”

“…Our predictions are consistent with a recently reported effect of increased ambient GABA on gamma oscillations in vivo, in which the gamma power was increased without changes in the firing frequency (9) (but see ref. 10). Assuming that changes in the power of oscillations and in their frequency can have different computational meanings (24), the effect of tonic GABA A conductance on pyramidal neurons can provide a mechanism enabling increases in the oscillation power without changes in their frequency.…”

“…GABA release by astrocytes also increases the gamma oscillation power in hippocampal area CA1 in vivo (9). Intriguingly, in hippocampal slices of animals lacking δ subunitcontaining GABA A receptors (which mediate tonic conductance in many local cell types including interneurons) the average frequency of cholinergically induced gamma oscillations is increased, whereas the oscillation power tends to drop (10). However, cellular mechanisms underlying such phenomena remain poorly understood.…”

Fast network oscillations in the hippocampus

“…The concept of synaptic inhibition representing a mere "braking action" (supporting the balance of excitation and inhibition) has evolved to a central organizational principle of coordinated network activity [32]. It now seems that the "balancing" function is provided by tonic inhibition to large extent, i.e., by a "background" local accumulation of GABA [33], while phasic (transient) inhibition seems to supply the temporal coordination of activity patterns [34,35,36]. A neuroscience topic currently under heavy investigation is the research on the remarkable heterogeneity of inhibitory interneurons.…”

Triphasic Dynamics of Stimulus-Dependent Information Flow between Single Neurons in Macaque Inferior Temporal Cortex

“…The frequency of gamma oscillation depends on the surrounding circuitry and its behavior (Atallah and Scanziani, 2009;Mann and Mody, 2010). Therefore, pair-by-pair variability of the peak frequencies might be expected to be larger in SUA-SUA coherence than those between MUAs or between MUA and LFP, since the variability of the surrounding circuit would be larger in the case of single-unit pairs compared with other configurations.…”